Abstract
For a development of a hybrid artificial liver, it is important to express liver specific functions at a high level, and to accomplish long-term maintenance of these functions. It has become clear that hepatocytes, which have a form of tissue-like structure (hepatocyte organoid), can express highly differentiated functions. In this study, we developed a novel module, which applied our original hepatocytes organoid culture technique using centrifugal force. And we investigated the performance of this module as a hybrid artificial liver.
The module consists of many hollow fibers arranged regularly at submillimeter order by spacers. Rat hepatocytes of 5.9 X 107 in number were immobilized inside or outside hollow fibers by centrifugal force. Each hollow fiber and its surrounding hepatocytes seemed to reconstruct a unit structure of a liver-lobule. The module performed perfusion culture and liver specific functions were evaluated.
Hepatocytes immobilized in the module formed an organoid surrounding hollow fibers with lotus-root shape. The hepatocyte organoid could express liver specific functions at high level, and maintain these functions for about 3∼5 months of culture. To evaluate as an artificial liver, the module was applied to a hepatic failure rat. The module was effective in supporting liver function and recovery from liver failure state. These results indicate that this novel module may be useful to treat liver failure patients until regeneration of the native liver.
